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S J De Souza

Publications and source records attributed to S J De Souza.

3 recordsLinked to original sources
PubMed1996

Collagen/collagenase interaction: does the enzyme mimic the conformation of its own substrate?

In this report, we present a hypothesis on the mechanism used by interstitial collagenases to cleave their natural substrate, interstitial collagens. The hypothesis is based on the assumption that the proline hinge domain of interstitial collagenase adopts a collagen-like conformation. With a collagen-like domain, the enzyme is able to disturb the quaternary organization of the triple helix in the collagenase-susceptible site. A modeling analysis suggests that interaction between prolines of both collagen and collagenase forming a kind of "proline zipper" is involved in the destabilization step. This destabilization makes the three-collagen helix susceptible to the catalytic cleft of the catalytic core.

Amino Acid Sequence↗
PubMed1992

Anti-platelet autoantibodies from ITP patients recognize an epitope in GPIIb/IIIa deduced by complementary hydropathy.

Idiopathic thrombocytopenic purpura (ITP) is a frequent platelet disorder due to the presence of anti-platelet autoantibodies. Recently a fibronectin/fibrinogen receptor in platelets, integrin GPIIb/IIIa, has been implicated as the antigen in chronic ITP. To examine the epitopes involved in the autoimmune response against GPIIb/IIIa we have used concepts from the complementary hydropathy principle. We used the peptide Trp-Thr-Val-Pro-Thr-Ala, WTVPTA (deduced from the complementary nucleotide sequence to that which codes for the Arg-Gly-Asp, RGD, domain in fibronectin), to test the immunologic activity of ITP sera. Sera from 31 patients with clinically defined ITP were tested in ELISA for reactivity towards WTVPTA and affinity purified GPIIb/IIIa. Seventeen sera (57%) reacted strongly with the glycoprotein complex, five of which reacted with the peptide. By affinity chromatography of one of these sera, we were able to show that antibodies that bind to the peptide are within the population that binds to GPIIb/IIIa. Liquid phase competition experiments revealed that binding of ITP serum to WTVPTA was inhibited only by a hydropathically compatible peptide. Our data indicate that autoantibodies can bind to hydropathically generated antigenic determinants and thus, render these peptides clinically important as diagnostic tools.

Adolescent↗